1. Field of the Invention
The present invention relates to an optical interrogation system and method capable of interrogating a two-dimensional (2D) array of optical sensors (e.g., grating coupled waveguide sensors) located for example in a microplate.
2. Description of Related Art
Today there is considerable interest in developing two-dimensional (2-D) optical sensor arrays and interrogation systems to enable Label Independent Detection (LID) of binding events, kinetic binding rates, and mass transports (cell-based assays) in a standard microplate format. These sensor arrays and measurement systems can be used to measure analyte-ligand binding events and rates (e. g. through biochemical interactions) and cellular mass transport (e.g. cell-based assays). The advantage of the standard microplate format is that it allows existing automated High Throughput Screening (HTS) and manual fluid handling systems to be used in conjunction with the sensors.
One type of label-independent interrogation system that can be used to detect binding events, kinetics, and mass transports using optical sensors (e.g., surface grating sensors) is known as an angular interrogation system. The angular interrogation system essentially monitors the output angle (or spatial shape) of light interacting with any particular optical sensor in order to determine the state of the sensor and thereby characterize any biochemical activity on the sensor's surface.
In order to accomplish this function, the angular interrogation system uses a narrowband spectral source such as a laser to emit a light beam which subsequently impinges upon the optical sensor. The optics of a launch arm tailor the optical characteristics (e.g., angular content, beam size, etc.) of this laser beam. Two mechanisms for directing the laser beam to the optical sensor in an angular interrogation system are: (1) scanning the incident angle of a collimated beam at the optical sensor; or (2) focusing a range of angles onto the optical sensor. In both cases, the goal is to determine the angular location and/or the angular shape of the sensor's resonant response and/or to detect changes in that resonant response. Toward this end, the angular interrogation system also has a receiver system that receives the optical response from the optical sensor and directs that response onto an optical detector.
If the optical detector of the angular system is placed some distance from the optical sensor, the angular shift and shape changes of the resonant response can be observed as a positional shift and change in the intensity of the received light across the plane of the optical detector. A computer can then process the measured response and algorithms can be used to characterize that response, thus enabling the detection of changes in the angle and shape of the resonant response from the optical sensor. In the case of surface sensors (e.g., surface waveguide grating sensors) the angular response provides sensitive information on a surface binding event, binding rate, and near surface mass transport.
The typical label-independent angular interrogation system is generally used to interrogate an array of optical sensors and not just one optical sensor as described above. Following are several patents, patent applications and publications that describe different types of angular interrogation systems which can be used to measure the angular responses from arrays of optical sensors.    1) U.S. Pat. No. 5,479,260, “Optical Process and Apparatus for Analysis of Substances on Sensor Surfaces,” C. Fattinger, Dec. 26, 1995.    2) U.S. Pat. No. 6,100,991, “Near Normal Incidence Optical Assaying Method and System having Wavelength and Angle Sensitivity,” Challener et al., Aug. 8, 2000.    3) “Grating couplers as chemical sensors: a new optical configuration,” A. Brandenburg and A. Gombert, Sensors and Actuators B, 17 (1993) 35-40.    4) “Real-time Measurement of Nucleic-acids Hybridization Using Evanescent-wave Sensors: Steps Towards the Genosensor,” F. Bier et al., Sensors and Actuators B 38-39, (1997) 78-82.    5) “A multilayer grating-based evanescent wave sensing technique,” W. A. Challener, et al., Sensors and Actuators B 71 (2000) 42-46    6) “Demonstration of Reverse Symmetry Waveguide Sensing in Aqueous Solutions,” R. Horvath et al., App. Phys. Lett., Vol 81, No 12, 16 Sep. 2002, pp 2166-2168    7) U.S. Pat. No. 6,346,376, “Optical Sensor Unit and Procedure for the Ultra-sensitive Detection of Chemical of Biochemical Analytes,” H. Sigrist et al., Feb. 12, 2002.    8) U.S. Pat. No. 6,429,022 B1, “Integrated-optical Sensor and Method for Integrated-optically Sensing Substance,” R. Kunz et al., Aug. 6, 2002.    9) U.S. Patent Application No. 2001/0026943 A1, “SPR Sensor System,” S. Dickopf et. al., Oct. 4, 2001.    10) U.S. Patent Application No. 2002/00001085 A1, “Set-up for Measuring Instruments for the Parallel Readout of SPR Sensors,” S. Dickopf et. al., Jan. 3, 2002.The contents of these documents are incorporated by reference herein.
Unfortunately, these traditional angular interrogation systems all suffer from one or more drawbacks. For instance, the traditional angular interrogation systems that scan or re-position the optical sensors or that move or switch critical optical components (such as the laser source) suffer from measurement errors due to errors in the motion and repeatability of positioning these critical components (see document nos. 6 and 7). The ensuing measurement errors due to the movement can then dominate the level of achievable measurement sensitivity. Furthermore, the act of scanning the angle or of moving, switching, or precisely re-positioning these critical components decreases the maximum array interrogation speed that is achievable by such angular interrogation systems.
In addition, some traditional angular interrogation systems use array size reduction or image reduction methods to direct optical responses from two dimensional arrays of optical sensors onto small area detectors (see document nos. 8 and 9). However, these types of traditional angular interrogation systems have resorted to scanning of the angle (or wavelength) to trace the sensor responses for the entire sensor array and as such they have problematic dynamic range, scanning speed, and/or scanning repeatability issues.
In fact, all traditional angular interrogation systems described to date must sacrifice one or more desirable attributes in order to achieve a high angular measurement sensitivity or a high 2-D array detection speed. Accordingly, there has been a need for an angular interrogation system that can address these shortcomings and other shortcomings of the traditional angular interrogation systems. These needs and other needs are satisfied by the angular interrogation system and method of the present invention.